A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib (INSIGHT)

• ClinicalTrials.gov Identifier: NCT05734105
• Recruitment Status: Recruiting
• First Posted: February 17, 2023
• Last Update Posted: May 20, 2024
• Sponsor: Deciphera Pharmaceuticals LLC
• Information provided by (Responsible Party): Deciphera Pharmaceuticals LLC

Tracking Information

• First Submitted Date: February 8, 2023
• First Posted Date: February 17, 2023
• Last Update Posted Date: May 20, 2024
• Actual Study Start Date: December 13, 2023
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 8, 2023)

Progression-free Survival (PFS) [ Time Frame: Up to end of treatment; up to approximately 48 months ]

The time from randomization until documented progressive disease (PD) based on IRR per mRECIST or death due to any cause, whichever occurs first.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 8, 2023)

• Objective Response Rate (ORR) [ Time Frame: Up to end of treatment; up to approximately 48 months ]
  Compare ORR by IRR of ripretinib vs sunitinib using mRECIST
• Overall Survival (OS) [ Time Frame: Up to approximately 48 months ]
  Compare OS of ripretinib vs sunitinib

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With Specific KIT Exon Mutations Who Were Previously Treated With Imatinib
• Official Title: An International, Phase 3, Randomized, Multicenter, Open-label Study of Ripretinib vs Sunitinib in Patients With Advanced GIST With KIT Exon 11 and Co-occurring KIT Exons 17 and/or 18 Mutations Who Were Previously Treated With Imatinib
• Brief Summary: This is a Phase 3, 2-arm, randomized, open-label, global, multicenter study comparing the efficacy of ripretinib to sunitinib in participants with GIST who progressed on first-line treatment with imatinib, harbor co-occurring KIT exons 11+17/18 mutations, and are without KIT exon 9, 13, or 14 mutations. Upon disease progression as determined by an independent radiologic review, participants randomized to sunitinib will be given the option to either crossover to receive ripretinib 150 mg QD or discontinue sunitinib.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: GIST

Intervention

• Drug: Ripretinib
  50 mg tablets
  Other Name: QINLOCK, DCC-2618
• Drug: Sunitinib
  12.5 mg tablets
  Other Name: Sutent

Study Arms

• Experimental: Ripretinib
  150 mg QD of ripretinib (3×50 mg tablets) will be dosed continuously in repeated 42-day cycles.
  Intervention: Drug: Ripretinib
• Active Comparator: Sunitinib
  50 mg QD of sunitinib (4×12.5 mg capsules) will be dosed in 42-day cycles. Sunitinib will be given continuously for 4 weeks with a 2-week break.
  Intervention: Drug: Sunitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 8, 2023): 54
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2027
• Estimated Primary Completion Date: February 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Male or female ≥18 years of age.
2. Histologic diagnosis of GIST with co-occurring KIT exons 11+17/18 mutations confirmed by ctDNA sample.
3. Participants must have advanced GIST and radiologic progression on imatinib treatment.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2 at screening.
5. Female participants of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug.
6. Participants of reproductive potential must agree to follow contraception requirements.
7. Participants must have at least 1 measurable lesion according to mRECIST v1.1 within 21 days prior to the first dose of study drug.
8. Adequate organ function and bone marrow reserve based on laboratory assessments performed at screening.
9. Resolution of all toxicities from prior therapy to Grade ≤1 (or participant baseline) within 1 week prior to the first dose of study drug.

Exclusion Criteria:

1. History of KIT exon 9 mutation or detection of KIT exon 9, 13, or 14 mutations in a ctDNA sample.
2. Has known active central nervous system metastases.
3. New York Heart Association Class II-IV heart disease, myocardial infarction within 6 months of Cycle 1 Day 1, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or congestive heart failure.
4. Use of strong or moderate inhibitors or inducers of cytochrome P450 (CYP) 3A prior to the first dose of study drug, and consumption of grapefruit or grapefruit juice within 14 days prior to the first dose of study drug.
5. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug.
6. Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, acute or chronic hepatitis B, or acute or chronic hepatitis C infection.

7. Gastrointestinal abnormalities including, but not limited to:

   1. inability to take oral medication
   2. malabsorption syndromes
   3. requirement for intravenous alimentation
8. Any active bleeding excluding hemorrhoidal or gum bleeding.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Team; 785-830-2100; Clinicaltrials@deciphera.com

• Listed Location Countries: Australia, Brazil, Canada, Chile, Germany, Italy, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05734105
• Other Study ID Numbers: DCC-2618-03-003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Deciphera Pharmaceuticals LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Deciphera Pharmaceuticals LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Team; Deciphera Pharmaceuticals LLC

• PRS Account: Deciphera Pharmaceuticals LLC
• Verification Date: May 2024